Genetic Variants and Vincristine-induced Neuropathy in Pediatric Cancer

Duscatleu Coviellom^*
*Correspondence: Duscatleu Coviellom, Department of Biochemistry and Molecular Biology, Stony Brook University, Stony Brook, NY 11794, USA, Email:

Introduction

Precision medicine represents a transformative approach in the management of childhood cancer, aiming to tailor treatments based on individual genetic profiles to enhance efficacy and minimize adverse effects. Among the various therapeutic agents used in pediatric oncology, vincristine—a widely utilized chemotherapeutic drug—plays a crucial role in treating a range of childhood cancers, including leukemia and lymphoma. However, vincristine is notorious for causing peripheral neuropathy, a debilitating side effect that can significantly impact the quality of life and overall treatment outcomes for young patients. The susceptibility to Vincristine-Induced Peripheral Neuropathy (VIPN) appears to be influenced by genetic factors, suggesting that genetic polymorphisms could be pivotal in determining an individual’s risk of developing this adverse effect. This study aims to explore the role of genetic variations in modulating the risk of VIPN in pediatric cancer patients, thereby advancing the field of precision medicine. By identifying specific genetic polymorphisms associated with increased susceptibility to VIPN, we seek to improve our understanding of the underlying mechanisms and to potentially guide more personalized therapeutic strategies that could mitigate this challenging side effect [1].

Description

Our study involved a comprehensive analysis of genetic data from pediatric cancer patients who received vincristine as part of their treatment regimen. We focused on identifying genetic polymorphisms that correlate with the development of VIPN, utilizing advanced genomic techniques such as Genome-Wide Association Studies (GWAS) and targeted sequencing. The cohort included patients with various types of childhood cancers, and we collected detailed clinical data on vincristine dosage, treatment duration, and the severity of neuropathic symptoms [1].

We employed statistical methods to analyze the association between specific genetic variants and the incidence and severity of VIPN. This included examining Single Nucleotide Polymorphisms (SNPs) and other genetic markers that might influence drug metabolism, neurotoxicity pathways, and individual responses to vincristine. Additionally, we explored potential geneenvironment interactions, assessing how genetic predispositions interact with factors such as drug dosage and patient-specific characteristics to influence neuropathy risk. The study also involved functional analyses to understand how identified genetic variants impact vincristine metabolism and neurotoxicity. This included assessing the expression levels of genes associated with drug metabolism and nerve function, and evaluating how genetic variations might alter these processes. Our goal was to create a comprehensive profile of genetic factors that contribute to VIPN, which could inform future research and clinical practices aimed at reducing the risk of this side effect [2].

In addition to identifying specific genetic polymorphisms linked to VIPN, our study also involved a thorough examination of the genetic mechanisms underlying these associations. We investigated how the identified genetic variants might affect the pharmacokinetics and pharmacodynamics of vincristine. For instance, we explored variations in genes related to drug transport and metabolism, such as those encoding cytochrome P450 enzymes and ATP-binding cassette transporters, which are known to influence drug efficacy and toxicity. Furthermore, we assessed how these genetic factors impact neuroinflammatory responses and neuronal damage, providing insights into the biological pathways that contribute to neuropathy [3].

We also conducted subgroup analyses to determine if certain genetic variants had differential effects based on factors such as age, sex, or cancer type. This stratification allowed us to identify whether specific populations of pediatric patients are more vulnerable to VIPN based on their genetic profiles. Our study also included a longitudinal component, where we tracked the progression of neuropathic symptoms over time to understand how genetic factors might influence both the onset and severity of VIPN throughout the course of treatment [4].

To complement our genetic analysis, we integrated clinical data with molecular findings to create a risk prediction model for VIPN. This model aimed to predict the likelihood of developing neuropathy based on individual genetic profiles and clinical parameters, potentially guiding treatment decisions and preventive strategies. Additionally, we sought to validate our findings in independent cohorts to ensure the robustness and generalizability of our results [5].

Conclusion

The investigation into the influence of genetic polymorphisms on vincristine-induced peripheral neuropathy in childhood cancer patients has provided valuable insights into the genetic underpinnings of this challenging side effect. Our findings highlight specific genetic variants associated with an increased risk of VIPN, which could pave the way for more personalized treatment approaches. By incorporating genetic screening into clinical practice, healthcare providers could better predict which patients are at higher risk for neuropathy and adjust vincristine dosing or consider alternative therapies accordingly. This precision medicine approach has the potential to enhance treatment outcomes and minimize the adverse effects of chemotherapy, ultimately improving the quality of life for pediatric cancer patients. Future research should continue to refine our understanding of the genetic factors involved and explore additional mechanisms that could contribute to VIPN. Such efforts will be crucial in advancing the field of pediatric oncology and ensuring that treatments are both effective and tailored to individual genetic profiles.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Siegel, Rebecca L., Angela N. Giaquinto and Ahmedin Jemal. "Cancer statistics, 2024."CA: A Cancer J Clinic74 (2024).

   Google Scholar, Crossref, Indexed at

2. Bo, Letao, Youyou Wang, Yidong Li and John ND Wurpel, et al. "The battlefield of chemotherapy in pediatric cancers."Cancer15 (2023): 1963.

   Google Scholar, Crossref, Indexed at

3. Erdmann, Friederike, Line Elmerdahl Frederiksen, Audrey Bonaventure and Luzius Mader, et al. "Childhood cancer: Survival, treatment modalities, late effects and improvements over time."Cancer Epidemiol71 (2021): 101733.

   Google Scholar, Crossref, Indexed at

4. Pui, Ching-Hon, Dario Campana, Deqing Pei and W. Paul Bowman, et al. "Treating childhood acute lymphoblastic leukemia without cranial irradiation."New Eng J Med360 (2009): 2730-2741.

   Google Scholar, Crossref, Indexed at

5. Zečkanović, Aida, Janez Jazbec and Marko Kavčič. "Centrosomal protein72 rs924607 and vincristine-induced neuropathy in pediatric acute lymphocytic leukemia: Meta-analysis."Future Sci OA6 (2020): FSO582.

   Google Scholar, Crossref, Indexed at